The primary objective of this project is to obtain a better understanding of the mechanism of action of morphine (M) and other analgesic drugs (e.g. met-enkephalin, ME) in mesencephalic reticular formation (MRF) of rats. Therefore, I plan to identify the nociceptive neurotransmitters and determine how M and ME affect their action. I also plan to determine if cGMP will have an effect opposite that of cAMP; cAMP reverses the blockade of the nociceptive stimulus (NS) evoked firing that is produced by M and ME. I plan to characterize M and ME opiate receptors in the MRF by comparing the effects of M and ME to the effects of other analgesic drugs (e.g. cyclazocine). I also plan to determine if the opiate receptors in the amygdala are those that are related to the physiological effects of ME but not M. I will also study how serotonin modulates changes in neuronal firing in the trigeminal nucleus and the MRF. I plan to use a computer based pattern analysis to study changes in the pattern of neuronal firing that are associated with a nociceptive stimulus and how M and ME modify these patterns. I plan to study the mechanism of tolerance and dependence of a cellular level in the MRF. Finally, I plan to identify areas that project to areas of MRF where the interacerebral injection of M will produce analgesia by injection HRP intracerebrally in these areas.